tbuckley/cabot-search huggingface dataset:
Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial
Authors: Anna Calvert, Gayatri Amirthalingam, Nick Andrews, Sneha Basude, Matthew Coleman, Hannah Cuthbertson, Anna England, Vanessa Greening, Bassam Hallis, Edward Johnstone, Christine E Jones, Konstantinos Karampatsas, Asma Khalil, Kirsty Le Doare, Mary Matheson, Elisabeth Peregrine, Matthew D Snape, Manu Vatish, Paul T Heath, Agnieszka Burtt, Wendy Byrne, Angelika Capp, Lotoyah Carty, Krina Chawla, Sarah Collins, Emily Cornish, Olwenn Daniel, Jessica Fretwell, Andrew Gorringe, Teresa Gubbins, Tom Hall, Susan Johnston, Uzma Khan, Suzy Lim, Nicki Martin, Ella Morey, Jude Mossop, Katie O'Brien, Nelly Owino, Deborah Powell, Laxmee Ramkhelawon, Helen Ratcliffe, Hannah Roberts, Fenella Roseman, Laura Sparks, Lorraine Stapley, Stephen Taylor, Fiona Walbridge, Rosie Watts, Susan J. Wellstead, Tabitha Wishlade
Journal: The Lancet Microbe (2023)
Missed Directives
Authors: Glenn S. Ross
Journal: Annals of Internal Medicine (2023)

On Being a PatientApril 2023Missed DirectivesGlenn S. Ross, MDGlenn S. Ross, MDSentara Medical Group, Newport News, VirginiaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-3199 Audio Reading - “Missed Directives” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Missed Directives” by Glenn S. Ross, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail My mother died the day before my 60th birthday, or at least she should have. My mother at age 88 had accumulated an array of chronic medical conditions, including advanced multifocal arthritis, COPD that was oxygen dependent by day and BiPAP dependent by night owing to carbon dioxide retention, hypertension, chronic anxiety, and a smattering of other ailments. Several years ago, she developed acute respiratory failure after a hip replacement and had to be placed on a ventilator and then reintubated when her first extubation was unsuccessful. From that moment forward, she was resolute in her desire never to be ... Author, Article, and Disclosure InformationAuthors: Glenn S. Ross, MDAffiliations: Sentara Medical Group, Newport News, VirginiaCorresponding Author: Glenn S. Ross, MD, Sentara Medical Group, 11803 Jefferson Avenue, Suite 140, Newport News, VA 23606; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Missed Directives” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Missed Directives” by Glenn S. Ross, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2023Volume 176, Issue 4Page: 580-581 ePublished: 18 April 2023 Issue Published: April 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Flashback Foreword: Pemetrexed and Cisplatin in Mesothelioma
Authors: Thomas E. Stinchcombe
Journal: Journal of Clinical Oncology (2023)

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. April 17, 2023 ARTICLE CITATION DOI: 10.1200/JCO.22.02720 Journal of Clinical Oncology - published online before print April 17, 2023 PMID: 37068376 Flashback Foreword: Pemetrexed and Cisplatin in Mesothelioma Thomas E. Stinchcombe , MD1,2xThomas E. StinchcombeSearch for articles by this author Show More 1Division of Medical Oncology, Duke Cancer Institute, Durham, NC2Associate Editor, Journal of Clinical Oncology, Alexandria, VA https://doi.org/10.1200/JCO.22.02720 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn 2003, Vogelzang et al1 published a phase III trial, which demonstrated a superior overall survival, time to progression, and response rate with cisplatin and pemetrexed compared with cisplatin in patients with malignant pleural mesothelioma. At the time this trial was performed, there were doubts about the efficacy of chemotherapy in this disease, and this trial validated chemotherapy as an effective treatment, and platinum-pemetrexed became the standard first-line treatment for the next 2 decades.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Pemetrexed and Cisplatin in MesotheliomaThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Thomas E. StinchcombeThis author is an Associate Editor for Journal of Clinical Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: EMD Serono, Janssen Oncology, Turning Point Therapeutics, Sanofi/Aventis, GlaxoSmithKline, Genentech/Roche, Daiichi Sankyo/Astra Zeneca, Takeda, Eisai/H3 Biomedicine, G1 Therapeutics, Spectrum PharmaceuticalsResearch Funding: AstraZeneca (Inst), Takeda (Inst), Regeneron (Inst), Seattle Genetics (Inst), Mirati Therapeutics (Inst), Genentech/Roche (Inst)No other potential conflicts of interest were reported. Companion Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma
CISH impairs lysosomal function in activated T cells resulting in mitochondrial DNA release and inflammaging
Authors: Jun Jin, Yunmei Mu, Huimin Zhang, Ines Sturmlechner, Chenyao Wang, Rohit R. Jadhav, Qiong Xia, Cornelia M. Weyand, Jorg J. Goronzy
Journal: Nature Aging (2023)
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Authors: Marie-Gabrielle Duperron, Maria J. Knol, Quentin Le Grand, Tavia E. Evans, Aniket Mishra, Ami Tsuchida, Gennady Roshchupkin, Takahiro Konuma, David-Alexandre Trégouët, Jose Rafael Romero, Stefan Frenzel, Michelle Luciano, Edith Hofer, Mathieu Bourgey, Nicole D. Dueker, Pilar Delgado, Saima Hilal, Rick M. Tankard, Florian Dubost, Jean Shin, Yasaman Saba, Nicola J. Armstrong, Constance Bordes, Mark E. Bastin, Alexa Beiser, Henry Brodaty, Robin Bülow, Caty Carrera, Christopher Chen, Ching-Yu Cheng, Ian J. Deary, Piyush G. Gampawar, Jayandra J. Himali, Jiyang Jiang, Takahisa Kawaguchi, Shuo Li, Melissa Macalli, Pascale Marquis, Zoe Morris, Susana Muñoz Maniega, Susumu Miyamoto, Masakazu Okawa, Matthew Paradise, Pedram Parva, Tatjana Rundek, Muralidharan Sargurupremraj, Sabrina Schilling, Kazuya Setoh, Omar Soukarieh, Yasuharu Tabara, Alexander Teumer, Anbupalam Thalamuthu, Julian N. Trollor, Maria C. Valdés Hernández, Meike W. Vernooij, Uwe Völker, Katharina Wittfeld, Tien Yin Wong, Margaret J. Wright, Junyi Zhang, Wanting Zhao, Yi-Cheng Zhu, Helena Schmidt, Perminder S. Sachdev, Wei Wen, Kazumichi Yoshida, Anne Joutel, Claudia L. Satizabal, Ralph L. Sacco, Guillaume Bourque, Quentin Le Grand, Mark Lathrop, Tomas Paus, Israel Fernandez-Cadenas, Qiong Yang, Bernard Mazoyer, Philippe Boutinaud, Yukinori Okada, Hans J. Grabe, Karen A. Mather, Reinhold Schmidt, Marc Joliot, M. Arfan Ikram, Fumihiko Matsuda, Christophe Tzourio, Joanna M. Wardlaw, Sudha Seshadri, Hieab H. H. Adams, Stéphanie Debette
Journal: Nature Medicine (2023)

Abstract Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults ( N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort ( N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.
Consensus recommendations on how to assess the quality of surgical interventions
Authors: Anja Domenghino, Carmen Walbert, Dominique Lisa Birrer, Milo A. Puhan, Pierre-Alain Clavien, Dieter Heuskel, Nancy Kwan Man, João Monteiro, Juan F. Perellon, Sara Pérez Martínez, Soraya Seedat, Frank Urbaniok, Jayson Woodbridge, Jeffrey Barkun, Michael P. W. Grocott, Samia Hurst, Christoph A. Meier, Tanja Stamm, Thomas Szucs, J. E. Tuttle, Han-Kwang Yang, Thomas Zeltner, Eyal Zimlichman, Florian Rüter, Jens Deerberg-Wittram, Lara Bloom, Marie-Pascale Pomey, Susan M. Webb, Felix Berlth, Jose M. Ramia, Roxane D. Staiger, Kathy Sienko, Marit S. de Vos, Henrik Kehlet, Philip C. Müller, Martin Fey, Susan O’Reilly, René Vonlanthen, Andrew C. von Eschenbach, Jeffrey V. Lazarus, Zeynep Or, Clifford Y. Ko, Mia Aurelia Huber, Jonathan Ives, Tanja Krones, Robert D. Truog, Sridhar Venkatapuram, Jad Abou-Khalil, Julio F. Fiore, Cesar A. Hincapié, Norihiro Kokudo, Timothy M. Pawlik, Mark Adams, Joel Armitage, Anne Lübbeke, Patricia Sánchez-Velázquez, Reto Schuepbach, Alicja Zientara, Marit Kalisvaart, Daniel A. Hofmaenner, Jean-Daniel Chiche, Alexander I. R. Jackson, S. Ramani Moonesinghe, Fariba Abbassi, Bernice Elger, Alexander Joeris, Fabia Rothenfluh, Felix Schneuwly, Yuki Seidler, Guru Sivaraman, Tala Ballouz, Ana Costa-Ramon, Rebecca A. Snyder, Mirriam Tyebally Fang, Claudia M. Witt
Journal: Nature Medicine (2023)
Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models
Authors: Justin Cosentino, Babak Behsaz, Babak Alipanahi, Zachary R. McCaw, Davin Hill, Tae-Hwi Schwantes-An, Dongbing Lai, Andrew Carroll, Brian D. Hobbs, Michael H. Cho, Cory Y. McLean, Farhad Hormozdiari
Journal: Nature Genetics (2023)
Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial
Authors: Zachary D. Crees, Michael P. Rettig, Reyka G. Jayasinghe, Keith Stockerl-Goldstein, Sarah M. Larson, Illes Arpad, Giulio A. Milone, Massimo Martino, Patrick Stiff, Douglas Sborov, Denise Pereira, Ivana Micallef, Gemma Moreno-Jiménez, Gabor Mikala, Maria Liz Paciello Coronel, Udo Holtick, John Hiemenz, Muzaffar H. Qazilbash, Nancy Hardy, Tahir Latif, Irene García-Cadenas, Abi Vainstein-Haras, Ella Sorani, Irit Gliko-Kabir, Inbal Goldstein, Debby Ickowicz, Liron Shemesh-Darvish, Shaul Kadosh, Feng Gao, Mark A. Schroeder, Ravi Vij, John F. DiPersio
Journal: Nature Medicine (2023)

Abstract Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34 + hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 10 6 CD34 + cells kg –1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P &lt; 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P &lt; 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34 + HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529
Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice
Authors: Kelcee A. Everette, Gregory A. Newby, Rachel M. Levine, Kalin Mayberry, Yoonjeong Jang, Thiyagaraj Mayuranathan, Nikitha Nimmagadda, Erin Dempsey, Yichao Li, Senthil Velan Bhoopalan, Xiong Liu, Jessie R. Davis, Andrew T. Nelson, Peter J. Chen, Alexander A. Sousa, Yong Cheng, John F. Tisdale, Mitchell J. Weiss, Jonathan S. Yen, David R. Liu
Journal: Nature Biomedical Engineering (2023)

Sickle-cell disease (SCD) is caused by an A·T-to-T·A transversion mutation in the β-globin gene (HBB). Here we show that prime editing can correct the SCD allele (HBB
NetGO 3.0: Protein Language Model Improves Large-Scale Functional Annotations
Authors: Shaojun Wang, Ronghui You, Yunjia Liu, Yi Xiong, Shanfeng Zhu
Journal: Genomics Proteomics & Bioinformatics (2023)

As one of the state-of-the-art automated function prediction (AFP) methods, NetGO 2.0 integrates multi-source information to improve the performance. However, it mainly utilizes the proteins with experimentally supported functional annotations without leveraging valuable information from a vast number of unannotated proteins. Recently, protein language models have been proposed to learn informative representations [e.g., Evolutionary Scale Modeling (ESM)-1b embedding] from protein sequences based on self-supervision. Here, we represented each protein by ESM-1b and used logistic regression (LR) to train a new model, LR-ESM, for AFP. The experimental results showed that LR-ESM achieved comparable performance with the best-performing component of NetGO 2.0. Therefore, by incorporating LR-ESM into NetGO 2.0, we developed NetGO 3.0 to improve the performance of AFP extensively. NetGO 3.0 is freely accessible at https://dmiip.sjtu.edu.cn/ng3.0.
Omics Views of Mechanisms for Cell Fate Determination in Early Mammalian Development
Authors: Lin-Fang Ju, Heng-Ji Xu, Yun-Gui Yang, Ying Yang
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract During mammalian preimplantation development, a totipotent zygote undergoes several cell cleavages and two rounds of cell fate determination, ultimately forming a mature blastocyst. Along with compaction, the establishment of apicobasal cell polarity breaks the symmetry of an embryo and guides subsequent cell fate choice. Although the lineage segregation of the inner cell mass (ICM) and trophectoderm (TE) is the first symbol of cell differentiation, several molecules have been shown to bias the early cell fate through their inter-cellular variations at much earlier stages, including the 2- and 4-cell stages. The underlying mechanisms of early cell fate determination have long been an important research topic. In this review, we summarize the molecular events that occur during early embryogenesis, as well as the current understanding of their regulatory roles in cell fate decisions. Moreover, as powerful tools for early embryogenesis research, single-cell omics techniques have been applied to both mouse and human preimplantation embryos and have contributed to the discovery of cell fate regulators. Here, we summarize their applications in the research of preimplantation embryos, and provide new insights and perspectives on cell fate regulation.
Identification of a duck H9N2 influenza virus possessing tri-basic hemagglutinin cleavage sites genetically close to the human H9N2 isolates in China, 2022
Authors: Feng Wen, Gaojie Chen, Jinyue Guo, Minhui Guan, Zhili Li, Hai Yu, Jianjun Li, Quan Liu, Shujian Huang
Journal: Journal of Infection (2023)
IL-12 and IL-23 pathway inhibition in inflammatory bowel disease
Authors: Bram Verstockt, Azucena Salas, Bruce E. Sands, Clara Abraham, Haim Leibovitzh, Markus F. Neurath, Niels Vande Casteele, Silvio Danese, Geert D’Haens, Lars Eckmann, William A. Faubion, Brian G. Feagan, Vipul Jairath, Christopher Ma, Saurabh Mehandru, Julian Panes, Florian Rieder, William J. Sandborn, Mark S. Silverberg, Marisol Veny, Severine Vermeire, Stefania Vetrano
Journal: Nature Reviews Gastroenterology & Hepatology (2023)
NF-κB is a critical mediator of post-mitotic senescence in oligodendrocytes and subsequent white matter loss
Authors: Judith Stefanie Schlett, Melanie Mettang, Aladdin Skaf, Pavel Schweizer, Alina Errerd, Ephraim Alemayehu Mulugeta, Tabea Melissa Hein, Konstantinos Tsesmelis, Miltiadis Tsesmelis, Ulrike F. G. Büttner, Heinrich Wendt, Alireza Abaei, Volker Rasche, Vivien Prex, Ester Nespoli, Najwa Ouali Alami, Daniel Tews, Paul Walther, Deniz Yilmazer-Hanke, Franz Oswald, Leda Dimou, Thomas Wirth, Bernd Baumann
Journal: Molecular Neurodegeneration (2023)

Inflammaging represents an accepted concept where the immune system shifts to a low-grade chronic pro-inflammatory state without overt infection upon aging. In the CNS, inflammaging is mainly driven by glia cells and associated with neurodegenerative processes. White matter degeneration (WMD), a well-known process in the aging brain, manifests in myelin loss finally resulting in motor, sensory and cognitive impairments. Oligodendrocytes (OL) are responsible for homeostasis and maintenance of the myelin sheaths, which is a complex and highly energy demanding process sensitizing these cells to metabolic, oxidative and other forms of stress. Yet, the immediate impact of chronic inflammatory stress like inflammaging on OL homeostasis, myelin maintenance and WMD remains open.To functionally analyze the role of IKK/NF-κB signaling in the regulation of myelin homeostasis and maintenance in the adult CNS, we established a conditional mouse model allowing NF-κB activation in mature myelinating oligodendrocytes. IKK2-CAPLP-CreERT2 mice were characterized by biochemical, immunohistochemical, ultrastructural and behavioral analyses. Transcriptome data from isolated, primary OLs and microglia cells were explored by in silico pathway analysis and validated by complementary molecular approaches.Chronic NF-κB activation in mature OLs leads to aggravated neuroinflammatory conditions phenocopying brain inflammaging. As a consequence, IKK2-CAPLP-CreERT2 mice showed specific neurological deficits and impaired motoric learning. Upon aging, persistent NF-κB signaling promotes WMD in these mice as ultrastructural analysis revealed myelination deficits in the corpus callosum accompanied by impaired myelin protein expression. RNA-Seq analysis of primary oligodendrocytes and microglia cells uncovers gene expression signatures associated with activated stress responses and increased post mitotic cellular senescence (PoMiCS) which was confirmed by elevated senescence-associated β-galactosidase activity and SASP gene expression profile. We identified an elevated integrated stress response (ISR) characterized by phosphorylation of eIF2α as a relevant molecular mechanism which is able to affect translation of myelin proteins.Our findings demonstrate an essential role of IKK/NF-κB signaling in mature, post-mitotic OLs in regulating stress-induced senescence in these cells. Moreover, our study identifies PoMICS as an important driving force of age-dependent WMD as well as of traumatic brain injury induced myelin defects.
Cardiac patches made of brown adipose-derived stem cell sheets and conductive electrospun nanofibers restore infarcted heart for ischemic myocardial infarction
Authors: Xinbo Wei, Li Wang, Cuimi Duan, Kai Chen, Xia Li, Ximin Guo, Peng Chen, Haifeng Liu, Yubo Fan
Journal: Bioactive Materials (2023)

Cell sheet engineering has been proven to be a promising strategy for cardiac remodeling post-myocardial infarction. However, insufficient mechanical strength and low cell retention lead to limited therapeutic efficiency. The thickness and area of artificial cardiac patches also affect their therapeutic efficiency. Cardiac patches prepared by combining cell sheets with electrospun nanofibers, which can be transplanted and sutured to the surface of the infarcted heart, promise to solve this problem. Here, we fabricated a novel cardiac patch by stacking brown adipose-derived stem cells (BADSCs) sheet layer by layer, and then they were combined with multi-walled carbon nanotubes (CNTs)-containing electrospun polycaprolactone/silk fibroin nanofibers (CPSN). The results demonstrated that BADSCs tended to generate myocardium-like structures seeded on CPSN. Compared with BADSCs suspension-containing electrospun nanofibers, the transplantation of the CPSN-BADSCs sheets (CNBS) cardiac patches exhibited accelerated angiogenesis and decreased inflammation in a rat myocardial infarction model. In addition, the CNBS cardiac patches could regulate macrophage polarization and promote gap junction remodeling, thus restoring cardiac functions. Overall, the hybrid cardiac patches made of electrospun nanofibers and cell sheets provide a novel solution to cardiac remodeling after ischemic myocardial infarction.